Summary of Work: The Comparative Pathobiology Group has focused its research on defining the pathogenesis/carcinogenesis of disorders affecting the reproductive tract of humans and rodents, and assessing the role of environmental and endogenous factors in the induction of these disorders. Our group has used archival mouse and human tissues to determine the presence of growth factors in uterine leiomyomas ("fibroids") and leiomyosarcomas in mice and women. Data from our studies show that TGF-a (mature form) is expressed exclusively in malignant uterine smooth muscle cell tumors (leiomyosarcomas) of mice. However, in benign uterine smooth muscle cell tumors (leiomyomas) of mice and women this growth factor is not present. Also, uterine LS in women do not express TGF-a. In mice, we have also found a positive correlation between TGF-a staining and immunoexpression of epidermal growth factor receptor, and increased cell proliferation as measured by the expression of proliferating cell nuclear antigen (PCNA) in the malignant uterine leiomyosarcomas. Studies to assess the immunoexpression of factors (Bcl- 2; Bax) possibly modulating cell survival and death in human uterine leiomyomas show that both positive and negative regulatory proteins of programmed cell death (apoptosis) are present in uterine leiomyomas in women, and that apoptosis does not appear to play a significant role in the development of these tumors.